Abstract
Microfluidics has proven to be an extraordinary working platform to mimic and study blood flow phenomena and the dynamics of components of the human microcirculatory system. However, the use of real blood increases the complexity to perform these kinds of in vitro blood experiments due to diverse problems such as coagulation, sample storage, and handling problems. For this reason, interest in the development of fluids with rheological properties similar to those of real blood has grown over the last years. The inclusion of microparticles in blood analogue fluids is essential to reproduce multiphase effects taking place in a microcirculatory system, such as the cell-free layer (CFL) and Fähraeus–Lindqvist effect. In this review, we summarize the progress made in the last twenty years. Size, shape, mechanical properties, and even biological functionalities of microparticles produced/used to mimic red blood cells (RBCs) are critically exposed and analyzed. The methods developed to fabricate these RBC templates are also shown. The dynamic flow/rheology of blood particulate analogue fluids proposed in the literature (with different particle concentrations, in most of the cases, relatively low) is shown and discussed in-depth. Although there have been many advances, the development of a reliable blood particulate analogue fluid, with around 45% by volume of microparticles, continues to be a big challenge.
Highlights
The interaction between synthetic microparticles and biological systems has been an important area of research in the last several years; for example, the development of artificial oxygen carriers to substitute red blood cells (RBCs) in the body [74,75,76,77,78], but it is beyond the main scope of the present review focused on blood particulate analogue fluids for in vitro studies
Carneiro et al [52] have been the only authors reporting in the literature this type of extensional rheology measurements for their proposed blood particulate analogue fluid, which is composed of the PDMS (6:4) particles suspended in an aqueous solution with 4 wt% sodium dodecyl sulfate (SDS), as mentioned previously
The results have shown that each carrier fluid introduces different tendencies in the cell free layer (CFL) thickness, both cases slightly close to that formed by healthy RBCs
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. There are difficulties associated with the use of in vitro blood, such as coagulation, sample storage, sample disposal, complex cleaning of microdevices used, etc., in addition to ethical and economic issues These drawbacks have promoted the increasing interest to develop fluids with rheological properties similar to real blood [5]. These fluids, in most cases, have dispersed rigid microparticles inside (polystyrene, nylon, etc.) These BMFs have been developed to comply, as faithfully as possible, with physical (density, viscosity, and particle size) and acoustic (speed, backscatter, and attenuation) properties for their specific use in the improvement and calibration of Doppler ultrasound.
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